For the majority of people with type 2 diabetes mellitus, management of hyperglycemia is improved using a mulit-faceted approach including of weight control and pharmaceutical therapy. The usage of insulin sensitizing drugs thiazolidinediones (TZDs) offers the hope of improving glycemic control while preserving beta cell function. An unfortunate and potentially long term problem is that TZD therapy causes weight and adipose gain in most patients. Two large studies (UKPDS and DCCT) have clearly shown that monotherapies for managing hyerpglycemia lose efficacy within 4-6 years and require change or addition of complementary therapies. Weight gain induced by TZD could further compromise insulin sensitivity in the long term. Conjugated linoleic acid is a naturally occurring oil (commercially available as Tonalin), that inhibits weight gain and adipose accumulation in experimental animals and has weight suppressive effects in human subjects who are overweight or obese. The goal of this R21 proposal is to develop a rigorous experimental approach for understanding the safety and efficacy for using CLA to complement TZD for improved management of type 2 diabetes. We hypothesize that when combined with TZD, CLA suppresses weight gain in men and women. This study will be a double-masked randomized, placebo-controlled study where 60 subjects will be divided into one of three groups: A, TZD + Placebo Oil; B TZD + low dose CLA; C, TZD + high dose CLA. The primary variable is the change in body weights compared between groups (low CLA, high CLA vs. 'placebo' supplement) from baseline to Week 32 of intervention. Secondary variables include changes in fat mass, lean mass, insulin sensitivity index, hepatic enzyme levels, edema, adverse effects, and levels of adipocytokines. Because dietary energy intake, appetite and physical activity may influence energy balance, each of these factors will also be measured. If effective and safe, the combination of CLA with TZD offers the possibility of a complementary agent to suppress weight gain and extend the efficacy of TZD. Furthermore, findings from this adequately powered and sufficient duration study will substantiate (or refute) claims that CLA is an effective dietary supplement in weight suppression. With sales of CLA reaching $ 220 million for 2004 and increasing each year, efficacy and safety of CLA require rigorous evaluation. [unreadable] [unreadable] [unreadable]